Researchers have found that diet-derived molecules known as metabolites may be the main drivers of early-onset colorectal cancer risk, especially those associated with red and processed meat, according to a recent study published by Jayakrishnan et al. in npj Precision Oncology.
Despite advancements in colorectal cancer screening, there may be a need for different approaches for younger patients. Dr. Suneel Kamath, a gastrointestinal oncologist at the Cleveland Clinic, suggests that a simple test to measure biomarkers could be more practical than annual colonoscopies for younger adults.
Previous research identified differences in metabolites and the gut microbiome between early- and average-onset colorectal cancer patients. However, the complexity of interactions between these factors, such as when gut bacteria consume metabolites and produce their own, adds challenges to understanding cancer risk.
In their recent study, researchers used AI to analyze large-scale metabolite and microbiome data sets, finding that diet was a significant factor. Co-lead author Dr. Naseer Sangwan emphasized that diet, rather than the gut microbiome, appears to be the primary driver of early-onset colorectal cancer risk.
The study highlights that it may be easier to assess at-risk patients by measuring blood metabolites rather than sequencing stool bacteria. Younger patients with colorectal cancer showed higher levels of metabolites linked to arginine and the urea cycle, which may be associated with long-term consumption of red and processed meats.
Researchers suggest that discussing diet with patients under 60 may be an effective strategy for colorectal cancer prevention. They plan to validate their findings with national data and explore whether specific diets or drugs could help prevent or treat early-onset colorectal cancer.
Background
Despite significant advances in monitoring and screening for colorectal cancer, there may be a need for different strategies when addressing younger patients.
“At the end of the day, it’s impractical to apply our care models for those over 60 to younger adults simply because we cannot give everyone in the system yearly colonoscopies,” explained Dr. Suneel Kamath, a gastrointestinal oncologist at the Cleveland Clinic and senior author of the study. “What is much more feasible is to give everyone in the system a simple test to measure a biomarker that determines their colorectal cancer risk. Then we can give the most at-risk individuals appropriate screening,” he added.
Earlier research has identified differences in the metabolites of early- versus average-onset colorectal cancer, and separate studies have highlighted distinctions in the gut microbiome between younger and older adults with colorectal cancer. However, the interplay of multiple factors, including interactions between gut bacteria and metabolites, adds layers of complexity to understanding cancer risk.
Study Methods and Results
The recent study provided a large-scale analysis of metabolite and microbiome data sets from patients treated for either early- or average-onset colorectal cancer. The researchers employed an artificial intelligence (AI) algorithm to integrate and analyze data from various studies, aiming to pinpoint the most significant factors for further investigation. The analysis revealed that differences in diet, as indicated by metabolites, accounted for a significant portion of the differences observed between early-onset and later-onset patients.
“Researchers … have begun to focus on the gut microbiome as a primary contributor to colorectal cancer risk, [b]ut our data clearly show that the main driver is diet,” emphasized Dr. Naseer Sangwan, co-lead author and Director of the Microbial Sequencing & Analytics Resource Core at the Cleveland Clinic. “We already know the main metabolites associated with [early]-onset risk, so we can now move our research forward in the correct direction,” he noted.
The study suggests that it may be easier to identify at-risk patients by counting the metabolites in their blood rather than sequencing bacterial DNA in their stool for different microbes. “It can actually be very complicated and difficult to change your microbiome. While it’s not always easy, it is much simpler to change your diet to prevent colorectal cancer,” explained Dr. Kamath.
Notably, younger patients with colorectal cancer had higher levels of metabolites linked to the production and metabolism of the amino acid arginine and the urea cycle compared with older patients. These differences may be associated with the long-term consumption of red and processed meats.
Conclusions
The researchers emphasize that one of the most effective strategies for individuals under age 60 to prevent colorectal cancer may be to discuss their diets with their physicians.
Currently, the researchers are analyzing national data sets to validate their findings in patients across the country. They anticipate discovering that arginine and urea cycle metabolites—and, by extension, the overconsumption of red and processed meats—will be elevated among younger patients with colorectal cancer nationwide. The researchers plan to explore whether specific diets or commercially available drugs that regulate arginine production and the urea cycle could help prevent or treat early-onset colorectal cancer.
Although further research is necessary to fully understand how dietary factors contribute to colorectal cancer, the findings may lead to adjustments in patient care. “Even though [we] knew before this study that diet is an important factor in colorectal cancer risk, [we] didn’t always discuss it with [our] patients during their first visit. There is so much going on, it can already be so overwhelming,” emphasized Dr. Kamath. “Now, [we can] make sure to bring it up [with our] patients, and to any healthy friends or family members they may come in with, to try and equip them with the tools they need to make informed choices about their lifestyle,” he concluded.
Read more : Colon Cancer
Disclosure: For full disclosures of the study authors, visit nature.com.
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